The main objectives of the proposed investigations are (1) to further elucidate the molecular, cellular and systemic features underlying the demonstrated suppression of ongoing IgE responses, in mice and dogs, by tolergenic conjugates of haptens and antigens with the hydrophilic polymers, polyvinyl alcohol (PVA) and monomethoxypolyethylene glycol (mPEG); (2) to elucidate and characterize both the genetic parameters and the idiotype network mechanisms which regulate the induction and propagation of the IgE antibody response; (3) to analyze the structure and mechanism of action of suppressor T (Ts) cell factors. To attain the first aim, conjugates of PVA and mPEG with haptens and antigens will be synthesized with a series of synthetic polymers differing in molecular weight; the conjugates will also differ in their epitope density and degree of substitution. For the second aim will be delineated the mechanisms by which Ig-CH linked V region genes, and other as yet unidentified backgroud genes, interface with or complement the Ir genes for the overall regulation of the IgE response to structurally related and well defined small molecular weight proteins. Furthermore, the ongoing study of the heteroclitic anti-NP/anti-NIP IgE responses will be extended for analysis of idiotype (id) network regulation of the IgE response in mice and for the characterization of id-positive and id-specific TS cells. The TS cells implicated in all the systems under investigation will be used as a source for the isolation and characterization of their soluble suppressor factor(s).